The aims of these experiments are to examine the possible mechanisms of the chemopreventive effects of selenium. Extensive experiments have documented the chemopreventive efficacy of selenium for a wide variety of epithelial tumors, however there is a dearth of information on the mechanisms of selenium action. Recent experiments have indicated the presence of several selenoproteins in rodent tissues. So far, there is no definitive information on the possible functions of these proteins. Our experiments have focused on a 60K dalton selenoprotein whose expression appears to be diminished in non-cycling cells. The experiments proposed herein will examine the expression of the 60K protein and several other parameters of selenium exposure in mammary preneoplasias with respect to dietary selenium levels and tumorigenic response. The possible synergistic effects of vitamin E and selenium will also be examined in the in vivo model system. The relationships between selenium concentration, 60K selenoprotein, general protein synthesis and protein phosphorylation will be examined in an in vitro model system using mouse mammary epithelial cells. The hypothesis that the chemopreventive effects of selenium on cell growth are mediated by modification of protein function will be pursued by examining protein phosphorylation and protein synthesis.
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